4 ms·

Exercise may help slow cognitive decline in some people with Parkinson’s disease

80 points by rustoo 6y ago

wrongdonf 6y ago
Recently it was shown that the chemical ISRIB can “undo” traumatic brain injury. It turns out that when you get a concussion, the mechanical stress results in a metabolic self defense mechanism being triggered. Everyone thought the neurons were dying but they were just themselves latent. ISRIB interferes with this defense mechanism, turning the neurons back on. And it turns out that this metabolic defense mechanism is triggered in many scenarios, not just concussion. I became involved in a group of people who were interested in taking ISRIB. We engaged in an effort to synthesize it, and along the way we dredged the internet for any information we could find about other people who had taken ISRIB — the molecule has been known about for a long time. There are a handful of plausible stories, and it appeared that ISRIB would have no effect in one person and be life changing for another, both seemingly healthy. The common pattern was increased intelligence, an insatiable appetite for new and novel information and a marked reduction in the amount of sleep needed to function. We eventually came into contact with a group of Russians. They had already synthesized it and taken it. They reported the same effects from the accounts we had found. They also reported, surprisingly, the development of a tolerance among those who took it repeatedly. One person had an episode of very realistic hallucinations, dreams that seemed real. Another person gave it to his grandmother who was sick with dementia. She became lucid again but died a day or two later. We speculated that one of the reasons cells turn themselves off is because they are too dysfunctional to operate — so turning them back on brings the benefit of having that signal again in the case of neurons but also revives any dangerous behavior that was being suppressed. We acquired ISRIB from the Russians and the first person to get it didn’t notice an effect although he didn’t take much. At this point I fell out of contact because I was having a medical emergency from experimenting with a totally unrelated compound. It nearly killed me, I spent weeks in the asylum and still have lingering effects. After that my shulgin itch became satisfied permanently. One interesting thing about cognitive diseases that are metabolically rooted like schizophrenia, dementia, etc is that there are simple ways to coax the cells into metabolizing carbohydrates correctly again, as this article demonstrates. There is also another kind of chemical completely that can be used for energy, beta hydroxy butyrate, totally bypassing the problem. The field of metabolic restoration is the next big thing for sure.
- loceng 6y ago
  If ISRIB works as well as research seems to suggest then we all need to keep an eye on it to make sure big pharma doesn't suppress it so then their own patentable products can exist in the market.
- okoslaatoo 6y ago
  What does "metabolizing carbohydrates correctly" mean in this context? What are the effects when carbohydrates do not metabolize correctly?
  - beowulfey 6y ago
    It is an inhibitor of whats called the Integrated Stress Response. A “normal” cell is one that uses glucose to create energy and create additional fuel for mitochondria to make LOTS of fuel (caveat- not every cell, this varies a lot, but often enough). This fuel is used to power everything and keep it working well. Under stress, a lot of that normal machinery is shut down, which means a neuron may not communicate anymore, as all these normal things need lots of energy. I am not as sure on this point, but I think stress generally means a cell takes in less glucose; it shuts down mitochondria, and overall produces less energy.
  - throwaway_kufu 6y ago
    Excessive blood sugar, then insulin spikes, and over time type 2 diabetes. It used to take a life time to acquire type 2 diabetes and historically it was called adult onset diabetes. The first case of type 2 diabetes in a child was only diagnosed in the 1983...now it’s common in children. Generally about 1/3 of the US is prediabetic, this population will generally also suffer from other chronic (metabolic) conditions like inflammation and obesity.
- _Microft 6y ago
  > Another person gave it to his grandmother who was sick with dementia. She became lucid again but died a day or two later. Lucidity before death has been reported before for patients suffering from dementia and other neurological illnesses, so this might have been coincidence. The term is "Terminal Lucidity" if you want to search for it. https://en.wikipedia.org/wiki/Terminal_lucidity https://en.wikipedia.org/wiki/Terminal_lucidity
_0qft 6y ago
I'm currently running 60min every 2 days, in the morning, with an empty stomach. Hard to say if it really does help with my depression or anxiety. I'm always seeking social activities.
- O_H_E 6y ago
  My personal experience and physiatrist says that it does. It doesn't have to be "the" solution for it to qualify to be "helpful". > I'm always seeking social activities. I am not sure if this was framed in a negative view, but social activities are also supposed to help with depression.
  - _0qft 6y ago
    Yes but social activities involve risk taking, feelings of rejection, effort and a lot of time, which will at times, generate anxiety and depression.
hannihanni 6y ago
No surprise!
Gatsky 6y ago
Waiting for a study showing exercise does not improve outcome X. Seriously, do we need any more positive exercise studies? If you are a mammal, then exercise is good for you, let’s be done with it.
- meiraleal 6y ago
  > let’s be done with it ... and start using this useful information to formulate public policies.
- chiefalchemist 6y ago
  We survived because of movement, and other natural attributes. "Progress" (i.e., a forced shift from proactive living entities to reactive consumers) comes along and suddenly our evolutionary past is denied (usually for profit). There's nothing wrong with profit, unless it is the primary measurement of success and progress. Of course there's collateral damage, we're denying a massive chunk of our evolutionary makeup, our very nature. Another study to confirm this? Perhaps we're not the advanced species we make ourselves out to be?
- _Microft 6y ago
  I disagree that conjectures are equal to knowledge. The results might not be unexpected but you never know until you actually take a closer look.
- kiba 6y ago
  The study is not very rigorous. A limitation of the study was that participants reported their own levels of physical activity, so there is the possibility that they would not remember their levels exactly. Instead of involving a RCT, we have a survey study.
- TheCoelacanth 6y ago
  That is a safe assumption if you are deciding whether or not to exercise, but that doesn't mean we have learned everything there is to learn about the effect of exercise.
Forge36 6y ago
So you're saying there's nothing we can do? /s https://medlineplus.gov/benefitsofexercise.html https://medlineplus.gov/benefitsofexercise.html https://www.mayoclinic.org/healthy-lifestyle/fitness/in-depth/exercise/art-20048389 https://www.mayoclinic.org/healthy-lifestyle/fitness/in-dept... Google's quick questions+answers: What are the 10 benefits of exercise? What are 20 benefits of exercise? More results What are 15 benefits of exercise? What are some benefits of exercise? How many minutes should you play or exercise every day? What are the 5 benefits of health and wellness? I'm curious how they could control for the general benefit of exercise or if it this study is more "parkinson's does not prevent benefit to exercise". I wonder if future generations will look back on this and say "they were exceedingly lazy to the point of serious mental disease and decline"
- bobthepanda 6y ago
  The easiest exercise to do is the kind that is routine and integrated into your routine so much you don’t even think about it. When I lived in New York I walked a few blocks to the bus stop, down the stairs to the train, down the stairs to another train, and then a few blocks to work. And that was just the commute; not counting walks to the coffee shop for a break, the walk to pick up lunch, the walk to the subway to the bar or a friend’s house after work, etc. The problem is that, at least in the US, most people walk within a building or from the door to the car and that’s about it, and then we have to create silly rituals like culty group bicycle classes or 10,000 steps challenges to actually get the minimum exercise in. We don’t necessarily need to go back to everyone working the fields all day levels of work, but the sedentary lifestyle in the US is not helping matters.
maxerickson 6y ago
researchers also found that greater physical activity at the start of the study lessened APOE e4-related cognitive decline two years later by an average of 0.007 points. So that sounds meaningless to me. Throw the numbers into the statistics machine I guess, but I bet a decline of 1.33 isn't meaningfully different than a decline of 1.323, even if you can confidently say you measured the difference.
DoreenMichele 6y ago
Exercise moves lymph out of the general tissues, though the brain only moves lymph in sleep. This is how the body "takes out the trash." Longer explanation in previous comment: https://news.ycombinator.com/item?id=25427090 https://news.ycombinator.com/item?id=25427090
tpoacher 6y ago
Conclusion: patients with higher levels of Parkinson's disease are less able to exercise.

80 points by rustoo 6y ago

Recently it was shown that the chemical ISRIB can “undo” traumatic brain injury. It turns out that when you get a concussion, the mechanical stress results in a metabolic self defense mechanism being triggered. Everyone thought the neurons were dying but they were just themselves latent. ISRIB interferes with this defense mechanism, turning the neurons back on. And it turns out that this metabolic defense mechanism is triggered in many scenarios, not just concussion. I became involved in a group of people who were interested in taking ISRIB. We engaged in an effort to synthesize it, and along the way we dredged the internet for any information we could find about other people who had taken ISRIB — the molecule has been known about for a long time. There are a handful of plausible stories, and it appeared that ISRIB would have no effect in one person and be life changing for another, both seemingly healthy. The common pattern was increased intelligence, an insatiable appetite for new and novel information and a marked reduction in the amount of sleep needed to function. We eventually came into contact with a group of Russians. They had already synthesized it and taken it. They reported the same effects from the accounts we had found. They also reported, surprisingly, the development of a tolerance among those who took it repeatedly. One person had an episode of very realistic hallucinations, dreams that seemed real. Another person gave it to his grandmother who was sick with dementia. She became lucid again but died a day or two later. We speculated that one of the reasons cells turn themselves off is because they are too dysfunctional to operate — so turning them back on brings the benefit of having that signal again in the case of neurons but also revives any dangerous behavior that was being suppressed. We acquired ISRIB from the Russians and the first person to get it didn’t notice an effect although he didn’t take much. At this point I fell out of contact because I was having a medical emergency from experimenting with a totally unrelated compound. It nearly killed me, I spent weeks in the asylum and still have lingering effects. After that my shulgin itch became satisfied permanently. One interesting thing about cognitive diseases that are metabolically rooted like schizophrenia, dementia, etc is that there are simple ways to coax the cells into metabolizing carbohydrates correctly again, as this article demonstrates. There is also another kind of chemical completely that can be used for energy, beta hydroxy butyrate, totally bypassing the problem. The field of metabolic restoration is the next big thing for sure.

loceng 6y ago
If ISRIB works as well as research seems to suggest then we all need to keep an eye on it to make sure big pharma doesn't suppress it so then their own patentable products can exist in the market.
okoslaatoo 6y ago
What does "metabolizing carbohydrates correctly" mean in this context? What are the effects when carbohydrates do not metabolize correctly?
- beowulfey 6y ago
  It is an inhibitor of whats called the Integrated Stress Response. A “normal” cell is one that uses glucose to create energy and create additional fuel for mitochondria to make LOTS of fuel (caveat- not every cell, this varies a lot, but often enough). This fuel is used to power everything and keep it working well. Under stress, a lot of that normal machinery is shut down, which means a neuron may not communicate anymore, as all these normal things need lots of energy. I am not as sure on this point, but I think stress generally means a cell takes in less glucose; it shuts down mitochondria, and overall produces less energy.
- throwaway_kufu 6y ago
  Excessive blood sugar, then insulin spikes, and over time type 2 diabetes. It used to take a life time to acquire type 2 diabetes and historically it was called adult onset diabetes. The first case of type 2 diabetes in a child was only diagnosed in the 1983...now it’s common in children. Generally about 1/3 of the US is prediabetic, this population will generally also suffer from other chronic (metabolic) conditions like inflammation and obesity.
_Microft 6y ago
> Another person gave it to his grandmother who was sick with dementia. She became lucid again but died a day or two later. Lucidity before death has been reported before for patients suffering from dementia and other neurological illnesses, so this might have been coincidence. The term is "Terminal Lucidity" if you want to search for it. https://en.wikipedia.org/wiki/Terminal_lucidity https://en.wikipedia.org/wiki/Terminal_lucidity

_0qft 6y ago

I'm currently running 60min every 2 days, in the morning, with an empty stomach. Hard to say if it really does help with my depression or anxiety. I'm always seeking social activities.

O_H_E 6y ago
My personal experience and physiatrist says that it does. It doesn't have to be "the" solution for it to qualify to be "helpful". > I'm always seeking social activities. I am not sure if this was framed in a negative view, but social activities are also supposed to help with depression.
- _0qft 6y ago
  Yes but social activities involve risk taking, feelings of rejection, effort and a lot of time, which will at times, generate anxiety and depression.

hannihanni 6y ago

No surprise!

Gatsky 6y ago

Waiting for a study showing exercise does not improve outcome X. Seriously, do we need any more positive exercise studies? If you are a mammal, then exercise is good for you, let’s be done with it.

meiraleal 6y ago
> let’s be done with it ... and start using this useful information to formulate public policies.
chiefalchemist 6y ago
We survived because of movement, and other natural attributes. "Progress" (i.e., a forced shift from proactive living entities to reactive consumers) comes along and suddenly our evolutionary past is denied (usually for profit). There's nothing wrong with profit, unless it is the primary measurement of success and progress. Of course there's collateral damage, we're denying a massive chunk of our evolutionary makeup, our very nature. Another study to confirm this? Perhaps we're not the advanced species we make ourselves out to be?
_Microft 6y ago
I disagree that conjectures are equal to knowledge. The results might not be unexpected but you never know until you actually take a closer look.
kiba 6y ago
The study is not very rigorous. A limitation of the study was that participants reported their own levels of physical activity, so there is the possibility that they would not remember their levels exactly. Instead of involving a RCT, we have a survey study.
TheCoelacanth 6y ago
That is a safe assumption if you are deciding whether or not to exercise, but that doesn't mean we have learned everything there is to learn about the effect of exercise.

Forge36 6y ago

So you're saying there's nothing we can do? /s https://medlineplus.gov/benefitsofexercise.html https://medlineplus.gov/benefitsofexercise.html https://www.mayoclinic.org/healthy-lifestyle/fitness/in-depth/exercise/art-20048389 https://www.mayoclinic.org/healthy-lifestyle/fitness/in-dept... Google's quick questions+answers: What are the 10 benefits of exercise? What are 20 benefits of exercise? More results What are 15 benefits of exercise? What are some benefits of exercise? How many minutes should you play or exercise every day? What are the 5 benefits of health and wellness? I'm curious how they could control for the general benefit of exercise or if it this study is more "parkinson's does not prevent benefit to exercise". I wonder if future generations will look back on this and say "they were exceedingly lazy to the point of serious mental disease and decline"

bobthepanda 6y ago
The easiest exercise to do is the kind that is routine and integrated into your routine so much you don’t even think about it. When I lived in New York I walked a few blocks to the bus stop, down the stairs to the train, down the stairs to another train, and then a few blocks to work. And that was just the commute; not counting walks to the coffee shop for a break, the walk to pick up lunch, the walk to the subway to the bar or a friend’s house after work, etc. The problem is that, at least in the US, most people walk within a building or from the door to the car and that’s about it, and then we have to create silly rituals like culty group bicycle classes or 10,000 steps challenges to actually get the minimum exercise in. We don’t necessarily need to go back to everyone working the fields all day levels of work, but the sedentary lifestyle in the US is not helping matters.

maxerickson 6y ago

researchers also found that greater physical activity at the start of the study lessened APOE e4-related cognitive decline two years later by an average of 0.007 points. So that sounds meaningless to me. Throw the numbers into the statistics machine I guess, but I bet a decline of 1.33 isn't meaningfully different than a decline of 1.323, even if you can confidently say you measured the difference.

DoreenMichele 6y ago

Exercise moves lymph out of the general tissues, though the brain only moves lymph in sleep. This is how the body "takes out the trash." Longer explanation in previous comment: https://news.ycombinator.com/item?id=25427090 https://news.ycombinator.com/item?id=25427090

tpoacher 6y ago

Conclusion: patients with higher levels of Parkinson's disease are less able to exercise.